Field of the Invention
The present invention relates to an oral delivery system for the treatment and/or prevention of periodontal, peri-implant and other bacterial and viral diseases or fungal diseases in the area of the mouth and throat as well as halitosis: i.e., infectious pathological changes.
Background Information
Infectious pathological changes occur very often and are the main reason for tooth loss/implant loss and halitosis in humans over 35 years of age. An infectious pathological change can be understood to mean an infection or inflammation of the gingival pocket, which, in several steps, can cause loss of the bone holding the tooth/implant. There are different degrees of severity of the condition. Lighter cases relate to the clinically termed gingivitis, whereas more severe cases are clinically called periodontitis/peri-implantitis.
Gingivitis is an inflammation of the gingiva (or of the gums), which is often caused by poor oral hygiene and/or the hormonal state of the patient. It is assumed that the untreated gingivitis develops into a periodontitis/peri-implantitis. Periodontitis is a bacterial disease which attacks the gingival tissue, the teeth, implants and the bone surrounding the teeth implants.
The oral cavity is a substantially aerobe environment through which saliva is flowing. In contrast, the periodontal/peri-implant microenvironment is rather anaerobic and plasma filtrate is flowing through it, which is called “gingival crevicular fluid”. The growth of microorganisms within this microenvironment is believed to be responsible for the occurrence of an infectious pathological change. Hence, treatment of said change is directed at monitoring and influencing said growth.
Trials in treating infectious pathological changes by agents which are administered into the oral cavity, such as antibacterial agents, have generally proved ineffective because the periodontal/peri-implant pocket is substantially inaccessible. On the other hand, the systemic administration of antibiotics has only little success in treating periodontal diseases.
Antibacterial agents, such as chlorhexidine and quaternary ammonium salts, in the form of mouth rinses have proved somewhat effective in the prophylaxis/treatment of infectious pathological changes. These agents, however, have different disadvantages. For instance, they are often accompanied by side effects, such as discoloration of the teeth, tongue, mucous membranes or of dental prostheses. Furthermore, these agents oft have a bad taste and affect the patient's sense of taste. Moreover, these agents often disturb wound healing. In addition, the agents are regularly absorbed by the mucous membranes or by the gastro-intestinal tract, which may lead to systemic effects. Further, toxic metabolites are often produced from the abovementioned agents. Another disadvantage lies in that the abovementioned agents usually have to be used at very high concentrations in order to achieve a corresponding effect. Further, allergenic potential was observed. Additionally, the abovementioned agents often have irritant effects and do not have particularly long shelf lives. Moreover, it was observed that blood and proteins influence the effects of these agents.
Pharmaceutical compositions which exhibit a release of agents and which can be introduced into the periodontal cavity and slowly release an antimicrobial agent have been developed. For example, U.S. Pat. Nos. 4,764,377 and 4,892,736 disclose the introduction of tetracycline into non-degradable polymeric fibers which can be wound around the teeth and release the antibiotic in the periodontal cavity over several days. However, the fibers must be fixed in their place with an adhesive and be removed again at the end of the treatment method.
U.S. Pat. No. 4,569,837 discloses the use of water-soluble polymeric substances (e.g., methyl cellulose, gelatin, etc.) as a polymeric matrix for a periodontal implant.
U.S. Pat. No. 5,002,769 discloses a biodegradable system for oral administration with delayed release for treating periodontal diseases. The agent is embedded into a matrix of hydrolyzed gelatin which is cross-linked with glutaraldehyde.
The above-described compositions show varying effectiveness in reducing the bacterial load in the periodontal pocket and in reducing the depth of the pocket. Moreover, these compositions often have the above-mentioned disadvantages.